Positive pressure ventilation is an important part of the therapy for newborns with respiratory failure, however, it can have adverse effects on cardiovascular function. Clinical experience suggests that such ventilation-induced hemodynamic effects may impact on the neurological outcome of these babies. We recognize that the incidence of brain hemorrhage increases when pressure ventilation is used. The relationship between positive pressure ventilation and brain blood flow remains an important factor in the outcome of these infants. I have shown that in newborn piglets brain blood flow is maintained even at high ventilation pressures despite a significant drop in cardiac output. My preliminary studies further suggest that brain blood flow during the period when cardiac output drops is influenced by prostanoids. This proposal is to further investigate factors controlling newborn cerebral perfusion when mechanical ventilation is used. The specific aims are: 1) investigate the relationship between prostanoid synthesis and cerebral hemodynamics during positive pressure ventilation; 2) establish the functional significance of this relationship; 3) investigate the interaction between prostanoids and other vasoactive systems known to increase prostanoid synthesis, and 4) begin to explore the possibility that leukotrienes affect cerebral hemodynamics during positive pressure ventilation. This work will be done in an established laboratory where present research is examining the role of prostanoids in controlling newborn cerebral perfusion. This application is to support further basic research training for an academic neonatologist in an established research environment. Both the Pediatric Department and the Physiology Department of The University of Tennessee, Memphis, are committed to providing the resources necessary to accomplish this goal.